Sequelae of giardiasis: an emerging public-health concern

Angel Escobedo

Sequelae of giardiasis: an emerging public-health concern

International Journal of Infectious Diseases, 2016

Editorial Sequelae of giardiasis: an emerging public health concern Although most individuals with a Giardia infection are asymptomatic, this pathogen is increasingly recognized as a cause of pathologies beyond the classical manifestations. 1 Morbidities associated with Giardia, including extra-intestinal manifestations and long-term consequences, have been identiﬁed increasingly over the past decades. 2–4 The importance of this pathogen in terms of patient well-being and its effect on quality of life, due to being a continuing cause of patient discomfort and pain, has been highlighted . 5 Unfortunately, giardiasis is not a health priority. This may be due to a lack of political will, funding, or interest from the scientiﬁc community (more focused on other scientiﬁc priorities), or to public indifference, but is most likely a combination of all of these factors. Nowadays, regardless of the stage of economic develop- ment of the affected countries, neglect of this protozoan disease is not the best option. Numerically speaking, giardiasis has never been a minor disease, even for many industrialized countries; thus, the sheer volume affected and the problems it causes warrant reﬂection regarding control strategies. The sequelae of Giardia infections are of considerable scientiﬁc interest as well as of public health signiﬁcance. Recently a large controlled prospective study of a cohort of individuals who had conﬁrmed Giardia infections during a waterborne outbreak in Norway was published. 6 In that study, a signiﬁcantly increased risk of both irritable bowel syndrome (IBS) and chronic fatigue (CF), even 6 years after the infection, was documented; fortunately, these decreased over time, indicating that Giardia may elicit very long-term, but slowly self-limiting complications. These data add to an all too slowly growing body of Giardia research, which, taken in aggregate, suggest that the time has come to encourage increased investigations. In this issue of the International Journal of Infectious Diseases, we present an analysis of the incidence of IBS without diarrhoea in the departments of Colombia during 2013. This was signiﬁcantly associated with the incidence of giardiasis (r 2 = 0.7457; p < 0.0001). Departments with higher giardiasis incidence had higher reported IBS (Figure 1), coinciding ecologically with the ﬁndings of the Norway study. Current discussion on the natural course of IBS and CF after Giardia infection has been enriched, whether manifested by classical signs and symptoms or a less straightforward clinical presentation . Important contributions have been made regarding the spectrum of illness attributable to giardiasis. It is illustrated that the potential development of sequelae may include both IBS and CF, in spite of the eradication of the organism. Additionally, this has opened new avenues of research. Further investigations on the pathogenic mechanisms behind the development of these two conditions are needed, which could lead to potential interventions to prevent them. This study also provides a clue to physicians whose patients do not respond with symptom resolution after successful therapy. They need to be aware of the potential sequelae of Giardia infection, to alert their patients of the possible importance of reporting a previous Giardia exposure when presenting for treatment if CF or IBS symptoms develop. In summary, there remains much to be known about Giardia and the spectrum of disease it causes, its epidemiology, and treatment. Collaborative studies that focus on determining precisely those who are most prone to develop CF or IBS after this infection are needed. Up to now, only old age and female sex have been identiﬁed as high risk factors for post-infectious fatigue. 7,8 It is also important to determine whether the treatment – and the timing of initiation – might inﬂuence these outcomes. International Journal of Infectious Diseases 49 (2016) 202–203 Figure 1. Non-linear regression model between giardiasis incidence rates (cases/ 100 000 population) and irritable bowel syndrome (IBS) incidence rates (cases/ 100 000 population) by department, Colombia, 2013. DOI of original article: http://dx.doi.org/10.1016/j.ijid.2016.06.005 Contents lists available at ScienceDirect International Journal of Infectious Diseases jou r nal h o mep ag e: w ww .elsevier .co m /loc ate/ijid http://dx.doi.org/10.1016/j.ijid.2016.06.008 1201-9712/ß 2016 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

According to previous studies, the continuation of symptoms post-elimination could be more frequent in those who have experienced chronic or treatment-refractory giardiasis. 9 Is there any therapeutic window for possible early intervention to avoid CF and/or IBS? Stratiﬁcation among patients susceptible to these complications according medical, immunological, and/or epide- miological proﬁles is needed to identify determinants of these clinical expressions. The Giardia isolates from patients developing long-term sequelae also deserve further study, as they may be genetically different. The study setting is also important when interpreting the results. It is also necessary to characterize the parasite genotype pattern in the region and to determine whether newly introduced genotypes could produce a synergistic interaction which could result in greater pathogenicity. Last, but not least, it is also important to evaluate the impact of Giardia infection and its post- infectious sequelae in low-income countries, where there is the greatest burden of disease and highest risk of transmission. Fortunately, research on giardiasis is growing, 10 since there is no doubt that for Giardia infection, there are still many questions to be answered. Up to now, the more you look, the more you ﬁnd. However, a question arises: ‘‘How much is there?’’ Funding: None. Ethical approval: Not required. Conﬂict of interest: The authors have no conﬂict of interest to disclose. References 1. Escobedo AA, Almirall P, Robertson LJ, Mørch K, Franco RM, Hanevik K, et al. Giardiasis: the ever present threat of a neglected disease. Infect Disord Drug Targets 2010;10:329–48. 2. Cantey PT, Roy S, Lee B, Cronquist A, Smith K, Liang J, et al. Study of nonoutbreak giardiasis: novel ﬁndings and implications for research. Am J Med 2011; 124:1175.e1–e8. 3. Halliez MC, Buret AG. Extra-intestinal and long term consequences of Giardia duodenalis infections. World J Gastroenterol 2013;19:8974–85. 4. Almirall P, Nu ´n ˜ez FA, Bello J, Gonza ´ lez OM, Ferna ´ ndez R, Escobedo AA. Abdom- inal pain and asthenia as common clinical features in hospitalized children for giardiasis. Acta Trop 2013;127:212–5. 5. Robertson LJ, Hanevik K, Escobedo AA, Mørch K, Langeland N. Giardiasis—why do the symptoms sometimes never stop? Trends Parasitol 2010;26:75–82. 6. Hanevik K, Wensaas KA, Rortveit G, Eide GE, Mørch K, Langeland N. Irritable bowel syndrome and chronic fatigue six years after Giardia infection: a controlled prospective cohort study. Clin Infect Dis 2014;59: 1394–400. 7. Mørch K, Hanevik K, Rortveit G, Wensaas KA, Langeland N. High rate of fatigue and abdominal symptoms 2 years after an outbreak of giardiasis. Trans R Soc Trop Med Hyg 2009;103:530–2. 8. Hanevik K, Kristoffersen EK, Sørnes S, Mørch K, Næss H, Rivenes AC, et al. Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome. BMC Infect Dis 2012;12:258. 9. Mørch K, Hanevik K, Rortveit G, Wensaas KA, Eide GE, Hausken T, et al. Severity of Giardia infection associated with post-infectious fatigue and abdominal symptoms two years after. BMC Infect Dis 2009;9:206. 10. Escobedo AA, Arencibia R, Vega RL, Almirall P, Rodrı ´guez-Morales AJ, Alfonso M. A bibliometric study of international scientiﬁc productivity in giardiasis cov- ering the period 1971-2010. J Infect Dev Ctries 2015;9:76–86. Angel A. Escobedo a,b,c Pedro Almirall c,d Se ´ rgio Cimerman c,e Alfonso J. Rodrı ´guez-Morales b,c,f, * a Academic Paediatric Hospital ‘‘Pedro Borra ´s’’, La Habana, Cuba b Working Group on Zoonoses, International Society for Chemotherapy, Aberdeen, UK c Committee on Clinical Parasitology, Panamerican Association of Infectious Diseases, La Habana, Cuba d Municipal Centre of Hygiene, Epidemiology and Microbiology ‘‘Plaza’’, La Habana, Cuba e Institute of Infectious Diseases ‘‘Emilio Ribas’’, Sa˜o Paulo, SP, Brazil f Research Group Public Health and Infection, Faculty of Health Sciences, Universidad Tecnolo ´gica de Pereira, Pereira, Risaralda, Colombia Corresponding Editor: Eskild Petersen, Aarhus, Denmark *Corresponding author. E-mail address: arodriguezm@utp.edu.co (A.J. Rodrı ´guez-Morales). 20 August 2015 Received in revised form 3 September 2015 Accepted 7 June 2016 Editorial / International Journal of Infectious Diseases 49 (2016) 202–203 203

International Journal of Infectious Diseases 49 (2016) 202–203 Contents lists available at ScienceDirect International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid Editorial Sequelae of giardiasis: an emerging public health concern Although most individuals with a Giardia infection are asymptomatic, this pathogen is increasingly recognized as a cause of pathologies beyond the classical manifestations.1 Morbidities associated with Giardia, including extra-intestinal manifestations and long-term consequences, have been identiﬁed increasingly over the past decades.2–4 The importance of this pathogen in terms of patient well-being and its effect on quality of life, due to being a continuing cause of patient discomfort and pain, has been highlighted .5 Unfortunately, giardiasis is not a health priority. This may be due to a lack of political will, funding, or interest from the scientiﬁc community (more focused on other scientiﬁc priorities), or to public indifference, but is most likely a combination of all of these factors. Nowadays, regardless of the stage of economic development of the affected countries, neglect of this protozoan disease is not the best option. Numerically speaking, giardiasis has never been a minor disease, even for many industrialized countries; thus, the sheer volume affected and the problems it causes warrant reﬂection regarding control strategies. The sequelae of Giardia infections are of considerable scientiﬁc interest as well as of public health signiﬁcance. Recently a large controlled prospective study of a cohort of individuals who had conﬁrmed Giardia infections during a waterborne outbreak in Norway was published.6 In that study, a signiﬁcantly increased risk of both irritable bowel syndrome (IBS) and chronic fatigue (CF), even 6 years after the infection, was documented; fortunately, these decreased over time, indicating that Giardia may elicit very long-term, but slowly self-limiting complications. These data add to an all too slowly growing body of Giardia research, which, taken in aggregate, suggest that the time has come to encourage increased investigations. In this issue of the International Journal of Infectious Diseases, we present an analysis of the incidence of IBS without diarrhoea in the departments of Colombia during 2013. This was signiﬁcantly associated with the incidence of giardiasis (r2 = 0.7457; p < 0.0001). Departments with higher giardiasis incidence had higher reported IBS (Figure 1), coinciding ecologically with the ﬁndings of the Norway study. Current discussion on the natural course of IBS and CF after Giardia infection has been enriched, whether manifested by classical signs and symptoms or a less straightforward clinical presentation . Important contributions have been made regarding the spectrum of illness attributable to giardiasis. It is illustrated DOI of original article: http://dx.doi.org/10.1016/j.ijid.2016.06.005 that the potential development of sequelae may include both IBS and CF, in spite of the eradication of the organism. Additionally, this has opened new avenues of research. Further investigations on the pathogenic mechanisms behind the development of these two conditions are needed, which could lead to potential interventions to prevent them. This study also provides a clue to physicians whose patients do not respond with symptom resolution after successful therapy. They need to be aware of the potential sequelae of Giardia infection, to alert their patients of the possible importance of reporting a previous Giardia exposure when presenting for treatment if CF or IBS symptoms develop. In summary, there remains much to be known about Giardia and the spectrum of disease it causes, its epidemiology, and treatment. Collaborative studies that focus on determining precisely those who are most prone to develop CF or IBS after this infection are needed. Up to now, only old age and female sex have been identiﬁed as high risk factors for post-infectious fatigue.7,8 It is also important to determine whether the treatment – and the timing of initiation – might inﬂuence these outcomes. Figure 1. Non-linear regression model between giardiasis incidence rates (cases/ 100 000 population) and irritable bowel syndrome (IBS) incidence rates (cases/ 100 000 population) by department, Colombia, 2013. http://dx.doi.org/10.1016/j.ijid.2016.06.008 1201-9712/ß 2016 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Editorial / International Journal of Infectious Diseases 49 (2016) 202–203 According to previous studies, the continuation of symptoms post-elimination could be more frequent in those who have experienced chronic or treatment-refractory giardiasis.9 Is there any therapeutic window for possible early intervention to avoid CF and/or IBS? Stratiﬁcation among patients susceptible to these complications according medical, immunological, and/or epidemiological proﬁles is needed to identify determinants of these clinical expressions. The Giardia isolates from patients developing long-term sequelae also deserve further study, as they may be genetically different. The study setting is also important when interpreting the results. It is also necessary to characterize the parasite genotype pattern in the region and to determine whether newly introduced genotypes could produce a synergistic interaction which could result in greater pathogenicity. Last, but not least, it is also important to evaluate the impact of Giardia infection and its postinfectious sequelae in low-income countries, where there is the greatest burden of disease and highest risk of transmission. Fortunately, research on giardiasis is growing,10 since there is no doubt that for Giardia infection, there are still many questions to be answered. Up to now, the more you look, the more you ﬁnd. However, a question arises: ‘‘How much is there?’’ Funding: None. Ethical approval: Not required. Conﬂict of interest: The authors have no conﬂict of interest to disclose. References 1. Escobedo AA, Almirall P, Robertson LJ, Mørch K, Franco RM, Hanevik K, et al. Giardiasis: the ever present threat of a neglected disease. Infect Disord Drug Targets 2010;10:329–48. 2. Cantey PT, Roy S, Lee B, Cronquist A, Smith K, Liang J, et al. Study of nonoutbreak giardiasis: novel ﬁndings and implications for research. Am J Med 2011; 124:1175.e1–e8. 3. Halliez MC, Buret AG. Extra-intestinal and long term consequences of Giardia duodenalis infections. World J Gastroenterol 2013;19:8974–85. 4. Almirall P, Núñez FA, Bello J, González OM, Fernández R, Escobedo AA. Abdominal pain and asthenia as common clinical features in hospitalized children for giardiasis. Acta Trop 2013;127:212–5. 5. Robertson LJ, Hanevik K, Escobedo AA, Mørch K, Langeland N. Giardiasis—why do the symptoms sometimes never stop? Trends Parasitol 2010;26:75–82. 203 6. Hanevik K, Wensaas KA, Rortveit G, Eide GE, Mørch K, Langeland N. Irritable bowel syndrome and chronic fatigue six years after Giardia infection: a controlled prospective cohort study. Clin Infect Dis 2014;59: 1394–400. 7. Mørch K, Hanevik K, Rortveit G, Wensaas KA, Langeland N. High rate of fatigue and abdominal symptoms 2 years after an outbreak of giardiasis. Trans R Soc Trop Med Hyg 2009;103:530–2. 8. Hanevik K, Kristoffersen EK, Sørnes S, Mørch K, Næss H, Rivenes AC, et al. Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome. BMC Infect Dis 2012;12:258. 9. Mørch K, Hanevik K, Rortveit G, Wensaas KA, Eide GE, Hausken T, et al. Severity of Giardia infection associated with post-infectious fatigue and abdominal symptoms two years after. BMC Infect Dis 2009;9:206. 10. Escobedo AA, Arencibia R, Vega RL, Almirall P, Rodrı́guez-Morales AJ, Alfonso M. A bibliometric study of international scientiﬁc productivity in giardiasis covering the period 1971-2010. J Infect Dev Ctries 2015;9:76–86. Angel A. Escobedoa,b,c Pedro Almirallc,d Sérgio Cimermanc,e Alfonso J. Rodrı́guez-Moralesb,c,f,* a Academic Paediatric Hospital ‘‘Pedro Borrás’’, La Habana, Cuba b Working Group on Zoonoses, International Society for Chemotherapy, Aberdeen, UK c Committee on Clinical Parasitology, Panamerican Association of Infectious Diseases, La Habana, Cuba d Municipal Centre of Hygiene, Epidemiology and Microbiology ‘‘Plaza’’, La Habana, Cuba e Institute of Infectious Diseases ‘‘Emilio Ribas’’, São Paulo, SP, Brazil f Research Group Public Health and Infection, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia Corresponding Editor: Eskild Petersen, Aarhus, Denmark *Corresponding author. E-mail address: arodriguezm@utp.edu.co (A.J. Rodrı́guez-Morales). 20 August 2015 Received in revised form 3 September 2015 Accepted 7 June 2016

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Sequelae of giardiasis: an emerging public-health concern